A reporter mouse for optical imaging of inflammation in mdx muscles

BACKGROUND: Duchenne muscular dystrophy (DMD) is due to mutations in the gene coding for human DMD; DMD is characterized by progressive muscle degeneration, inflammation, fat accumulation, and fibrosis. The mdx mouse model of DMD lacks dystrophin protein and undergoes a predictable disease course. While this model has been a valuable resource for pre-clinical studies aiming to test therapeutic compounds, its utility is compromised by a lack of reliable biochemical tools to quantifiably assay muscle disease. Additionally, there are few non-invasive assays available to researchers for measuring early indicators of disease progression in mdx mice. METHODS: Mdx mice were crossed to knock-in mice expressing luciferase from the Cox2 promoter. These reporter mice (Cox2(FLuc/+)DMD(−/−)) were created to serve as a tool for researchers to evaluate muscle inflammation. Luciferase expression was assayed by immunohistochemistry to insure that it correlated with muscle lesions. The luciferase signal was quantified by optical imaging and luciferase assays to verify that the signal correlated with muscle damage. As proof of principle, Cox2(FLuc/+)DMD(−/−) mice were also treated with prednisolone to validate that a reduction in luciferase signal correlated with prednisone treatment. RESULTS: In this investigation, a novel reporter mouse (Cox2(FLuc/+)DMD(−/−) mice) was created and validated for non-invasive quantification of muscle inflammation in vivo. In this dystrophic mouse, luciferase is expressed from cyclooxygenase 2 (Cox2) expressing cells and bioluminescence is detected by optical imaging. Bioluminescence is significantly enhanced in damaged muscle of exercised Cox2(FLuc/+)DMD(−/−) mice compared to non-exercised Cox2(FLuc/+)DMD(+/+) mice. Moreover, the Cox2 bioluminescent signal is reduced in Cox2(FLuc/+)DMD(−/−) mice in response to a course of steroid treatment. Reduction in bioluminescence is detectable prior to measurable therapy-elicited improvements in muscle strength, as assessed by traditional means. Biochemical assay of luciferase provides a second means to quantify muscle inflammation. CONCLUSIONS: The Cox2(FLuc/+)DMD(−/−) mouse is a novel tool to evaluate the therapeutic benefits of drugs intended to target inflammatory aspects of dystrophic pathology. This mouse model will be a useful adjunct to traditional outcome measures in assessing potential therapeutic compounds

The Essential Interactions in Oxides and Spectral Weight Transfer in Doped Manganites

We calculate the value of the Fr\"ohlich electron-phonon interaction in manganites, cuprates, and some other charge-transfer insulators and show that this interaction is much stronger than any relevant magnetic interaction. A polaron shift due to the Fr\"ohlich interaction, which is about 1 eV, suggests that carriers in those systems are small (bi)polarons at all temperatures and doping levels, in agreement with the oxygen isotope effect and other data. An opposite conclusion, recently suggested in the literature, is shown to be incorrect. The frequency and temperature dependence of the optical conductivity of ferromagnetic manganites is explained within the framework of the bipolaron theory.Comment: 6 pages, REVTeX 3.1 with 3 eps-figures. Journal versio

The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors.

Recently, we reported that toll-like receptor (TLR)2 and TLR4 localized on the glomerular endothelium in the glomeruli of streptozotocin (STZ)-induced type 1 diabetic mice and high fat diet feed-induced type 2 diabetic mice, and that periodontal pathogen Porphyromonas gingivalis LPS (Pg-LPS) administration lowered the survival rate of diabetic mice. The present study aims to examine the effect of TLR4 blocking on the suppression of Pg-LPS-induced diabetic nephropathy.The survival rate and morphological/biochemical features for streptozotocin-induced diabetic mice with Pg-LPS and TLR4 blocker eritoran administration were investigated by reporter gene assay, urine and blood analysis, immunohistochemistry, and real time-PCR.All of the diabetic mice administered Pg-LPS were euthanized within the survival period of almost all of the diabetic mice. The blood urea nitrogen and creatinine, expression of TLR2 and TGF-b, and type 1 collagen accumulation, in the diabetic mice increased significantly with the Pg-LPS administration. In spite of the limited TLR4 activation with Pg-LPS, the TLR4 blocker eritoran decreased blood urea nitrogen and creatinine, and raised the survival rate of the Pg-LPS-administered diabetic mice slightly. The high expression levels of TLR2, TGF-b, and type 1 collagen in Pg-LPS-administered diabetic mice decreased with eritoran. Nuclear STAT3 which enhances TLR2 expression was detected in the TLR2-expressing glomeruli of diabetic mice. The TLR2 and STAT3 gene expression increased by the Pg-LPS administration but decreased with eritoran. These may suggest that Pg-LPS-induced diabetic nephropathy is mainly dependent on TLR2 signaling on glomerular endothelial cells, and that TLR4 blocker eritoran may play a role to slow the progress of diabetic nephropathy.福岡歯科大学2017年

Performance studies of the Belle II Silicon Vertex Detector with data taken at the DESY test beam in April 2016

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations

Performance studies of the Belle II Silicon Vertex Detector with data taken at the DESY test beam in April 2016

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations

The Belle II SVD detector

The Silicon Vertex Detector (SVD) is one of the main detectors in the Belle II experiment at KEK, Japan. In combination with a pixel detector, the SVD determines precise decay vertex and low-momentum track reconstruction. The SVD ladders are being developed at several institutes. For the development of the tracking algorithm as well as the performance estimation of the ladders, beam tests for the ladders were performed. We report an overview of the SVD development, its performance measured in the beam test, and the prospect of its assembly and commissioning until installation

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets